The effect of modified Qiyuan paste on mice with low immunity and sleep deprivation by regulating GABA nerve and immune system.

BACKGROUND: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. METHODS: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin-eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. RESULTS: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. CONCLUSIONS: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Presence of PD-1 similarity genes in monocytes may promote the development of type 1 diabetes mellitus and poor prognosis of pancreatic cancer.

INTRODUCTION: To identify proteins and corresponding genes that share sequential and structural similarity with programmed cell death protein-1 (PD-1) in patients with type 1 diabetes mellitus (T1DM) via bioinformatics analysis. RESEARCH DESIGN AND METHODS: All proteins with immunoglobulin V-set domain were screened in the human protein sequence database, and the corresponding genes were obtained in the gene sequence database. GSE154609 was downloaded from the GEO database, which contained peripheral blood CD14+ monocyte samples from patients with T1DM and healthy controls. The difference result and the similar genes were intersected. Analysis of gene ontology and Kyoto encyclopedia of genes and genomes pathways was used to predict potential functions using the R package 'cluster profiler'. The expression differences of intersected genes were analyzed in The Cancer Genome Atlas pancreatic cancer dataset and GTEx database using t-test. The correlation between the overall survival and disease-free progression of patients with pancreatic cancer was analyzed using Kaplan-Meier survival analysis. RESULTS: 2068 proteins with immunoglobulin V-set domain similar to PD-1 and 307 corresponding genes were found. 1705 upregulated differentially expressed genes (DEGs) and 1335 downregulated DEGs in patients with T1DM compared with healthy controls were identified. A total of 21 genes were overlapped with the 307 PD-1 similarity genes, including 7 upregulated and 14 downregulated. Of these, mRNA levels of 13 genes were significantly increased in patients with pancreatic cancer. High expression of MYOM3 and HHLA2 was significantly correlated with shorter overall survival of patients with pancreatic cancer, while high expression of FGFRL1, CD274, and SPEG was significantly correlated with shorter disease-free survival of patients with pancreatic cancer. CONCLUSIONS: Genes encoding immunoglobulin V-set domain similar to PD-1 may contribute to the occurrence of T1DM. Of these genes, MYOM3 and SPEG may serve as potential biomarkers for the prognosis of pancreatic cancer.

Polyunsaturated fatty acids drive neutrophil extracellular trap formation in nonalcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Non-resolving inflammation, triggered by sustained accumulation of lipids, is an important driving force of NASH. Thus, unveiling metabolic immune regulation could help better understand the pathology and intervention of NASH. In this study, we found the recruitment of neutrophils is an early inflammatory event in NASH mice, following the formation of neutrophil extracellular traps (NETs). NET is an initiating factor which exacerbates inflammatory responses in macrophages. Inhibition of NETs using DNase I significantly alleviated inflammation in NASH mice. We further carried out a metabolomic study to identify possible metabolic triggers of NETs, and linoleic acid (LA) metabolic pathway was the most altered pathway. We re-analyzed published clinical data and validated that LA metabolism was highly correlated with NASH. Consistently, both LA and γ-linolenic acid (GLA) were active in triggering NETs formation by oxidative burst. Furthermore, we identified silybin, a hepatoprotective agent, as a potent NETosis inhibitor, which effectively blocked NETs formation both in vitro and in vivo. Together, this study not only provide new insights into metabolism-immune causal link in NASH progression, but also demonstrate silybin as an important inhibitor of NETs and its therapeutical potential in treating NETosis-related diseases.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Bile acids target mitofusin 2 to differentially regulate innate immunity in physiological versus cholestatic conditions.

Systemic metabolites serving as danger-associated molecular patterns play crucial roles in modulating the development, differentiation, and activity of innate immune cells. Yet, it is unclear how innate immune cells detect systemic metabolites for signal transmission. Here, we show that bile acids function as endogenous mitofusin 2 (MFN2) ligands and differentially modulate innate immune response to bacterial infection under cholestatic and physiological conditions. Bile acids at high concentrations promote mitochondrial tethering to the endoplasmic reticulum (ER), leading to calcium overload in the mitochondrion, which activates NLRP3 inflammasome and pyroptosis. By contrast, at physiologically relevant low concentrations, bile acids promote mitochondrial fusion, leading to enhanced oxidative phosphorylation and thereby strengthening infiltrated macrophages mediated phagocytotic clearance of bacteria. These findings support that bile acids, as endogenous activators of MFN2, are vital for tuning innate immune responses against infections, representing a causal link that connects systemic metabolism with mitochondrial dynamics in shaping innate immunity.

Dendrobium officinalis Six Nostrum Promotes Intestinal Urate Underexcretion via Regulations of Urate Transporter Proteins in Hyperuricemic Rats.

BACKGROUND: Dendrobium officinalis Six nostrum (DOS) can be prepared by adding Dendrobium officinalis into Simiao Wan in accordance with the Traditional Chinese Medicine (TCM) theory and other previous findings. Our previous study has shown that DOS treatment can lead to a marked decrease in Serum UA (SUA) levels. The purpose of this study was to explore the effects of DOS on intestinal UA excretion in hyperuricemia and its underlying mechanisms. METHODS: DOS was administered intragastrically to hyperuricemic rats induced by oral administration of HX and PO for 7 weeks. The SUA level, fecal UA and XOD activity were detected. The expressions of UA transporters (ABCG2, GLUT9, and PDZK1), CNT2, and tight junction proteins (ZO- 1 and claudin-1) in the intestine were assayed by IHC staining. The serum LPS and DAO levels were detected by ELISA kits. The intestinal histological changes were assessed using H&E staining. RESULTS: DOS treatment decreased the SUA level while markedly increasing the fecal UA level by 28.85%~35.72%. Moreover, DOS effectively up-regulated the expression of ABCG2 and PDZK1 and down-regulated the expression of GLUT9 in the intestine. DOS markedly decreased the serum LPS level by 21.4%~32.1% and DAO activity by 12.3%~19.7%, which in turn ameliorated the intestinal pathology. As a result, it could protect intestinal barrier function, as indicated by the increase of villus height (V), the reduction of the crypt depth (C), and the elevation of the V/C ratio. It also increased the expression of ZO-1 and claudin-1. In addition, DOS significantly down-regulated the expression of CNT2, which reduced purine nucleoside transportation from the intestine into the blood, and inhibited XOD activity, leading to a decrease in UA production. CONCLUSION: DOS exerted anti-hyperuricemic effects via regulation of intestinal urate transporters and could protect intestinal barrier function by restoring the expressions of ZO-1 and claudin-1.

Association between type 2 diabetes and 5-year overall survival in early-stage pancreatic cancer: a retrospective cohort study.

Background: This study examined the association between type 2 diabetes mellitus (T2DM) and 5-year overall survival (OS) in patients with pancreatic cancer (PC). Methods: This retrospective cohort study included patients diagnosed with stage I/II PC at Shengjing Hospital of China Medical University from January 2012 to December 2017. All patients had pancreatic ductal adenocarcinoma or its subtypes. The outcome was the 5-year OS rate based on data from the patient charts. Data analysis was performed using SPSS 22.0. Results: A total of 238 patients were included: 72 with T2DM and 166 without T2DM. There were significant differences in blood glucose levels and OS between the two groups (all P < 0.05). The median OS was 11.4 (95% confidence interval CI [8.49-14.31]) months in the T2DM group and 16.3 (95% CI [12.44-20.16], P = 0.023) months in the non-T2DM group. After adjustment for confounders, T2DM was an independent factor affecting 5-year OS (P = 0.010). Compared with non-T2DM patients, T2DM patients had a higher risk of death (HR = 1.475, 95% CI [1.096-1.985]). Conclusions: T2DM is associated with 5-year OS in patients with PC.

Congenital lipoid adrenal hyperplasia with Graves' disease: A case report.

BACKGROUND: Congenital adrenal hyperplasia (CAH), which is caused by a mutation of the steroidogenic acute regulatory (StAR) gene. Affected patients are usually characterized by adrenal insufficiency in the first year of life, salt loss, glucocorticoid and mineralocorticoid deficiency, and female external genitalia, regardless of chromosomal karyotype. Patients with non-classical lipoid CAH usually develop glucocorticoid deficiency and mild mineralocorticoid deficiency at 2-4 years of age. CASE SUMMARY: Herein, We report the case of a woman with non-classic lipoid CAH combined with Graves' disease. Her chromosome karyotype was 46, XX, and high-throughput sequencing revealed two missense variants in the StAR gene: c.229C > T (p.Q77X) and c.814C > T (p.R272C), which were inherited from both parents (non-close relatives). The patient was treated for Graves' disease in a timely manner and the dosage of glucocorticoid was adjusted during the treatment of Graves' disease. CONCLUSION: This is the first case of non-classic lipoid CAH combined with Graves' disease reported in the Chinese population. In addition to conventional glucocorticoid replacement therapy, timely adjustments were made to the dosages of thyroid hormone and glucocorticoid to avoid adrenal crisis as a consequence of the increased demand and accelerated metabolism of glucocorticoids when the patient was diagnosed with Graves' disease.

The beneficial effects of Polygonatum sibiricum Red. superfine powder on metabolic hypertensive rats via gut-derived LPS/TLR4 pathway inhibition.

BACKGROUND: Metabolic hypertension (MH) is characterized by elevated blood pressure accompanied by metabolic abnormalities, with the gut-derived lipopolysaccharide/toll like receptor 4 (LPS/TLR4) pathway an important triggering mechanism. The conventional Chinese plant Polygonatum sibiricum Red. is traditionally used as a medicinal and edible food source. Currently, several studies have examined its anti-obesity and anti-diabetic actions, with potential roles for MH treatment; however, specific P. sibiricum Red. roles in MH and associated mechanisms remain unclear. OBJECTIVES: Our purpose was to identify the effects and mechanisms of P. sibiricum Red. superfine powder (PSP) in a MH rat model triggered by high sugar and high fat compounds in an excessive alcohol diet (ACHSFDs). METHODS: A MH rat model was induced by ACHSFDs, and PSP was administered daily at 0.5 and 1.0 g/kg doses, respectively. Firstly, the effects of PSP on MH were assessed using blood pressure, serum lipid, and lipid deposition assays in the liver. Changes in intestinal flora were detected by high-throughput 16S rRNA sequencing, while metabolite short-chain fatty acids (SCFAs) and LPS levels were quantified by gas chromatography (GC) and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin & eosin (H&E) staining and transmission electron microscopy (TEM) were performed to evaluate histopathological changes in the rat colon. d-lactic acid (d-LA) levels and tight junction proteins (TJPs) expression were also measured to assess intestinal barrier function. Also, aortic endothelial microstructures, serum endothelin 1 (ET-1), and nitric oxide (NO) levels were investigated to determine vascular endothelial function. Finally, the TLR4/MyD88 signaling pathway in the aorta and gut was evaluated by western blotting, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Blood pressure and blood lipid metabolism disorders induced by ACHSFDs in MH rats were improved by PSP administration. Intestinal flora analyses revealed decreased SCFAs and LPS levels following PSP administration, which was accompanied by increased Streptococcus species levels and decreased Desulfobacter and Desulfovibrio species levels. PSP increased SCFAs levels, and the expression of SCFAs receptors GPCR41 and GPCR43 in the colon. Meanwhile, the expression of tight junction proteins (TJPs) such as Claudin-1, occludin were upregulated in the ileum and colon, while TLR4 and MyD88 were downregulated, thereby strengthening intestinal barrier integrity and reducing serum LPS levels. Additionally, PSP treatment improved vascular endothelial function by inhibiting the TLR4/MyD88 pathway in vessels, improving vascular endothelial cell shedding, and regulating the NO and ET-1 balance. CONCLUSIONS: We demonstrated the beneficial effects and potential mechanisms of PSP in our MH rat model. Based on gut microbiota structure modulation and intestinal barrier improvements, PSP inhibited LPS-induced vascular TLR4/MyD88 signaling activation to improve vascular endothelial function, which in turn reduced blood pressure. Our study provides valuable insights on PSP therapy for MH.

Bile acid restrained T cell activation explains cholestasis aggravated hepatitis B virus infection.

Cholestasis is a common complication of hepatitis B virus (HBV) infection, characterized by increased intrahepatic and plasma bile acid levels. Cholestasis was found negatively associated with hepatitis outcome, however, the exact mechanism by which cholestasis impacts anti-viral immunity and impedes HBV clearance remains elusive. Here, we found that cholestatic mice are featured with dysfunctional T cells response, as indicated by decreased sub-population of CD25+ /CD69+ CD4+ and CD8+ cells, while CTLA-4+ CD4+ and CD8+ subsets were increased. Mechanistically, bile acids disrupt intracellular calcium homeostasis via inhibiting mitochondria calcium uptake and elevating cytoplasmic Ca2+ concentration, leading to STIM1 and ORAI1 decoupling and impaired store-operated Ca2+ entry which is essential for NFAT signaling and T cells activation. Moreover, in a transgenic mouse model of HBV infection, we confirmed that cholestasis compromised both CD4+ and CD8+ T cells activation resulting in poor viral clearance. Collectively, our results suggest that bile acids play pivotal roles in anti-HBV infection via controlling T cells activation and metabolism and that targeting the regulation of bile acids may be a therapeutic strategy for host-virus defense.

Polysaccharide, the Active Component of Dendrobium officinale, Ameliorates Metabolic Hypertension in Rats via Regulating Intestinal Flora-SCFAs-Vascular Axis.

Metabolic hypertension (MH) is the most common type of hypertension worldwide because of unhealthy lifestyles, such as excessive alcohol intake and high-sugar/high-fat diets (ACHSFDs), adopted by humans. Poor diets lead to a decrease in the synthesis of short-chain fatty acids (SCFAs), which are produced by intestinal flora and transferred by G protein-coupled receptors (GPCRs), resulting in impaired gastrointestinal function, disrupted metabolic processes, increased blood pressure (BP), and ultimately, MH. It is not clear whether Dendrobium officinale polysaccharide (DOPS) can mediate its effects by triggering the SCFAs-GPCR43/41 pathway. In this study, DOPS, with a content of 54.45 ± 4.23% and composition of mannose, glucose, and galacturonic acid at mass percentages of 61.28, 31.87, and 2.53%, was isolated from Dendrobium officinale. It was observed that DOPS, given to rats by intragastric administration after dissolution, could lower the BP and improve the abnormal lipid metabolic processes in ACHSFD-induced MH rats. Moreover, DOPS was found to increase the production, transportation, and utilization of SCFAs, while improving the intestinal flora and strengthening the intestinal barrier, as well as increasing the intestinal levels of SCFAs and the expression of GPCR43/41. Furthermore, DOPS improved vascular endothelial function by increasing the expression of GPCR41 and endothelial nitric oxide synthase in the aorta and the nitric oxide level in the serum. However, these effects were all reversed by antibiotic use. These findings indicate that DOPS is the active component of Dendrobium officinale, and it can reverse MH in rats by activating the intestinal SCFAs-GPCR43/41 pathway.

Effect of nicotinamide N-methyltransferase on lipid accumulation in 3T3-L1 adipocytes.

Nicotinamide N-methyltransferase (NNMT) is a methylase, and its expression is positively correlated with obesity and insulin resistance. This study aims to detect the effects of NNMT on lipid accumulation, triglyceride content, adipocyte differentiation-related transcription factors, genes related to lipid metabolism, adipokine expression, and autophagy in adipocytes. Lentivirus vectors and eukaryotic expression plasmids were used to interfere with NNMT expression. The Oil Red O method was used to detect lipid accumulation, and colorimetry was used to detect triglyceride levels. The transcription of adipocyte differentiation-related transcription factors (PPARγ, C/EBPα, and SREBP1), lipid metabolism-related genes (FABP4, FAS, FATP1 [SLC27A1], and LPL), adipokines (ADIPOQ and LEP) and autophagy-related genes (Beclin1, ATG7, ATG12, and ATG14) was detected by quantitative real-time polymerase chain reaction (RT-qPCR), and the protein expressions of PPARγ, ADIPOQ, LC3I, LC3II, Beclin1, and P62 were detected by western blot analysis. Compared with the control group, the knockdown of NNMT expression reduced lipid accumulation and triglyceride content in 3T3-L1 cells. The transcription of PPARγ, C/EBPα, SREBP1, FABP4, FASN, FATP1, LPL, Beclin1, ATG7, ATG12, and ATG14 decreased, while ADIPOQ and LEP transcription increased. The expression of PPARγ, LC3I/II, and Beclin1 proteins also decreased, while ADIPOQ and P62 protein expression increased. The over-expression NNMT group showed experimental results opposite to those described above. Interference with the expression of NNMT affects lipid accumulation, triglyceride content after cell differentiation, adipocyte differentiation-related transcription factors, genes related to lipid metabolism, the expression of adipokines, and autophagy in adipocytes.

Octreotide-based therapies effectively protect mice from acute and chronic gastritis.

Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori-induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin, Il-6 and Il1b expression through induction of Muc5ac and Occludin, significantly improving hyperacidity and gastric bleeding. As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2, decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis.

Comparison of Protective Effects of Shenmai Injections Produced by Medicinal Materials from Different Origins on Cardiomyocytes.

Shenmai injection is mainly used for the treatment of heart-related diseases, including coronary heart disease, viral myocarditis, chronic cor pulmonale, and shock in Asia. Medicinal materials from different origins produce Shenmai injections for clinical use, and their protective effects on cardiomyocytes may vary with the choice of raw materials. In this study, we compared the protective effects of Shenmai injections produced from different raw materials on cardiomyocytes. Results showed that the protective effects of various Shenmai injections on hypoxia-reoxygenation-induced cardiomyocyte injury were mainly attributed to total ginsenosides extract, with few differences between them. However, the protective effects of different Shenmai injections on doxorubicin and oxidative stress-induced cardiomyocyte injury were significantly different; the protective effects of Shenmai injection with Zhejiang Ophiopogon japonicus as raw material were significantly better than those with Sichuan Ophiopogon japonicus, consistent with our previous research results. Our study reveals the different cardiomyocyte protective effects of Shenmai injections produced by medicinal materials from different origins, laying a scientific foundation for their clinical selection.

The Prognostic Role of Glycemia in Patients With Pancreatic Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Fasting blood glucose and glycated hemoglobin (HbA1c) levels are associated with the risk of pancreatic cancer. AIM: To examine the relationship between perioperative glucose and HbA1c levels and prognosis in patients with pancreatic cancer. METHODS: PubMed, Embase, and the Cochrane Library were queried for potentially eligible studies published up to May 2021. The exposures were perioperative fasting glucose and HbA1c levels. The primary outcome was survival. The secondary outcome was complications. All analyses were performed using the random-effects model. RESULTS: Ten studies (48,424 patients) were included. The pre-operative (HR=1.10, 95%CI: 0.89-1.35; I2 = 45.1%, Pheterogeneity=0.078) and postoperative (HR=1.19, 95%CI: 0.92-1.54; I2 = 67.9%, Pheterogeneity=0.001) blood glucose levels were not associated with the survival to pancreatic cancer. Similar results were observed for HbA1c (HR=1.09, 95%CI: 0.75-1.58; I2 = 64.2%, Pheterogeneity=0.039), fasting blood glucose (FBG)/HbA1c (HR=1.16, 95%CI: 0.67-1.68; I2 = 0.0%, Pheterogeneity=0.928), and FBG (HR=1.75, 95%CI: 0.81-3.75; I2 = 79.4%, Pheterogeneity=0.008). Pre-operative blood glucose levels were not associated with postoperative complications (OR=0.90, 95%CI: 0.52-1.56), but postoperative glucose levels were associated with postoperative complications (OR=3.06, 95%CI: 1.88-4.97; I2 = 0.0%, Pheterogeneity=0.619). CONCLUSION: Blood glucose, FBG, and HbA1c levels are not associated with the survival of patients with pancreatic cancer. Postoperative blood glucose levels could predict postoperative complications.

Ganluyin ameliorates DSS-induced ulcerative colitis by inhibiting the enteric-origin LPS/TLR4/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), that is associated with a significantly increased risk of colon cancer. As a classic traditional Chinese medicine, Ganluyin (GLY) has a long history as an anti-inflammatory medication, but its impacts on UC has not been established. AIM OF THE STUDY: This study aims to evaluate the protective effect and mechanism of GLY on a pathway involving enteric-origin lipopolysaccharide (LPS), toll-like receptor (TLR)4, and NF-κB in mice with dextran sulfate sodium (DSS)-induced UC. MATERIALS AND METHODS: After three weeks of intragastric administration of GLY, a UC model was induced in mice by administration of 4% DSS in drinking water for one week. The disease activity index (DAI) was measured, and histological staining was used to detect histopathological changes of colon. LPS content of the serum was measured by ELISA, and the expression of tight junction proteins and proteins related to TLR4/NF-κB pathway in colon were analyzed by immunohistochemistry or Western Blotting. The intestinal flora was analyzed by 16S rRNA sequencing. RESULTS: GLY improved the histological pathological changes of DSS-induced UC, as assessed by DAI, colonic mucosal damage, inflammatory cell infiltration, and goblet cell and mucus reduction. GLY also protected the intestinal mucosal barrier by increasing the expression of the tight junction proteins, occludin, claudin-1, and ZO-1 and by reducing the serum LPS content and decreasing the expression of TLR4, MyD88, NF-κB, IL-6, IL-1ß, and TNF-α proteins in colon. Analyses of the intestinal flora showed that GLY restored the homeostasis of the intestinal flora through increases in the abundance of Firmicutes and decreases in the abundance of Proteobacteria and Bacteroidetes, which is associated with the production of LPS. CONCLUSION: GLY might exert an anti-UC effect by improving the colonic mucosal barrier and inhibiting the enteric-origin LPS/TLR4/NF-κB inflammatory pathway, and restoring the homeostasis of the intestinal flora in UC mice. These discoveries lay a strong foundation for GLY as a UC treatment.

Effects of Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Fructose and Potassium Oxonate.

AIMS AND OBJECTIVES: Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating Uric Acid (UA) levels. Our previous studies have confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UAlowering effect of DoMRE on both UA production and excretion. MATERIALS AND METHODS: Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the Serum Uric Acid (SUA) and Creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expressions of Urate Transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-Binding Cassette Superfamily G member 2 (ABCG2) were assessed using immune-histochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine. RESULTS: Fructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expressions of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion. CONCLUSION: DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.

Acupuncture versus Lornoxicam in the Treatment of Acute Renal Colic: A Randomized Controlled Trial.

OBJECTIVE: To compare the analgesic efficacy and safety of acupuncture and lornoxicam in acute renal colic (ARC). DESIGN SETTING PARTICIPANT: A randomized, double-blind, parallel-controlled, single-centered trial was conducted at Susong County People's Hospital from October 2019 to November 2020. Eighty-four patients with ARC were randomly divided into lornoxicam group (Group L) and acupuncture group (Group A). Group A was treated with acupuncture at Sanyinjiao (SP6), Yinlingquan (SP9) and normal saline, and Group L was treated with sham acupuncture at SP6, SP9 and lornoxicam. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) scores and adverse reactions such as nausea and dizziness were recorded within 5, 10, 15, 20 and 40 minutes after treatment. The main outcome of this study was the short-term effective (STE) rate, the secondary outcome was the onset time, and the safety index was incidence of adverse reactions. RESULTS: A total of 80 patients completed this study, including 41 patients (21 males and 20 females) in Group L and 39 patients (21 males and 18 females) in Group A. Group A exhibited lower scores versus group L after treatment (P < 0.05). The overall STE of group L was 61.00% (25/41), significantly lower than group A [84.62% (33/39)] (P < 0.001). There was no difference in the incidence of adverse reactions between group A [2.6% (1/39)] and group L [7.3% (3/41)] (P = 0.616). The ordered logistic regression analysis showed patients receiving acupuncture therapy are more likely to be cured [OR = 2.887, 95% CI: (1.190, 7.000), P = 0.019]. CONCLUSION: Acupuncture at SP6, SP9 and intramuscular injection of lornoxicam can effectively and safely relieve ARC, but the former has faster and better analgesic effect. Moreover, the incidence of adverse reactions was similar between the two treatments. This acupuncture therapy is recommended as a complementary therapy for ARC.

Ginsenosides regulation of lysophosphatidylcholine profiles underlies the mechanism of Shengmai Yin in attenuating atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) preparation, Shengmai Yin (SMY), is widely applied in cardiovascular disease treatments. However, the pharmacological mechanism of its therapeutic effects has not been fully clarified. AIM OF THIS STUDY: This study aimed to clearly define the efficacy and underlying mechanism of SMY and its active components in protecting against atherosclerosis. MATERIALS AND METHODS: The pharmacological effects of SMY and its components were evaluated upon a mouse hypercholesteremia model induced by a high cholesterol diet (HCD) for 12 weeks and Apoe-/- mice, a mouse atherosclerosis model. Pathological indicators including serum cholesterol levels, cytokines and histological changes in aortic root plaques were assessed. Untargeted metabolomic, untargeted lipidomic and targeted lipidomic changing profiles were investigated to clarify pharmacological mechanisms. RESULTS: SMY and red ginseng crude extracts (GE) significantly decreased the serum cholesterol levels in hypercholesteremia mice and reduced the aortic root plaque areas and exerted antiatherogenic efficacy in Apoe-/- mice. Moreover, total red ginseng saponin extracts (TGS) showed the most apparent improvement on maintaining lipid homeostasis, representing the effects of red ginseng in SMY on atherosclerosis treatment. Mechanically, TGS inhibited serum secreted phospholipase A2 (sPLA2) activity and lowered the serum levels of lysophosphatidylcholine (lysoPC), which is a risk factor for atherosclerosis. CONCLUSIONS: Our findings revealed that ginsenosides from SMY exerted therapeutic effects on atherosclerosis by maintaining lipid homeostasis including cholesterol and lysoPCs.